Interferon‐γ is not an antiviral, but a growth‐promoting factor for t lymphocytes

Abstract

The effects of interferon (IFN)-gamma or IFN-alpha/beta on virus yield, (2'-5')oligo(A) synthetase activation, H-2 antigen expression and proliferation of T lymphocytes have been investigated. Under the culture conditions used, vesicular stomatitis virus or Semliki Forest virus replication in T cells was not impaired by the addition of IFN-gamma, whereas it was completely inhibited by the addition of IFN-alpha/beta. In contrast, B cell lines, macrophage-transformed cell lines and fibroblasts were fully protected by both IFN-gamma as well as IFN-alpha/beta following virus infection. The lack of sensitivity of T lymphocytes to the antiviral effects of IFN-gamma was not due to absence of specific membrane receptors, since in saturation binding experiments with 125I-labeled murine IFN-gamma most T cell lines displayed a number of binding sites and a degree of affinity comparable to those found on B cells, which are fully sensitive to IFN-gamma antiviral activity. Analysis of IFN-induced dsRNA-dependent (2'-5')oligo(A) synthetase activity, one of the biochemical markers for cellular responses to IFN, showed that it was not induced in T lymphocytes after IFN-gamma treatment, whereas IFN-alpha/beta induced high levels. Both IFN-gamma and IFN-alpha/beta enhanced H-2 antigen expression on T cells as well as on cells of different histological type. Moreover, when IFN-gamma was tested for its antiproliferative activity on T cells, it was found to consistently potentiate the response of these cells to mitogens or growth factors, rather than inhibit their proliferation. Taken as a whole these results suggest that on T lymphocytes IFN-gamma should not be regarded as an antiviral agent, but rather as a modulator of T cell growth and functional differentiation, transducing intracellular signals dissimilar to those observed with target cells of different origin.

Persistent Virus Infection despite Chronic Cytotoxic T-Lymphocyte Activation in Gamma Interferon-Deficient Mice Infected with Lymphocytic Choriomeningitis Virus

“…Thus, the failure to eliminate the virus in LCMV Armstrong-infected IFN-␥ Ϫ/Ϫ mice is not caused by failure of effector cell generation. This observation confirms our recent interpretation that the collapse of the LCMV-specific CTL response noted in LCMV Traub-infected, IFN-␥ Ϫ/Ϫ mice is an immunopathological event and not the result of a requirement for IFN-␥ in effector cell differentiation as suggested by others (20,46). At 3 months p.i.…”

Influenza Virus-specific T Cells Lead to Early Interferon in Lungs of Infected Hosts: Development of a Sensitive Radioimmunoassay

“…The effects we noted on the reduction of infectious influenza virus by transferred T cells may be due to the direct antiviral activity of IFN-~,, although this is not thought to be a major function of this particular species of IFN (e.g. Landolfo et al, 1988). Interferons ~ and fl are known to be potent antiviral agents and IFN-a peaks in the lungs of influenza-infected mice on day 4 (Wyde et al, Short communication 1982).…”

An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.

“…Furthermore, induction of ICSBP mRNA by IFN-y appears to occur mainly in cells of the immune system. IFN-'y is produced by T cells and, through a distinct receptor, modulates lymphoid functions including macrophage superoxide production (40), macrophage migration (30,31), T-cell proliferative activity (41), lymphokine production (40), and lymphokine function (39). The prevalence of ICSBP mRNA expression in the immune tissues and its selective inducibility by IFN-y in cells of lymphocyte/ macrophage lineages suggest that ICSBP plays a regulatory role in cells of the immune system.…”